Disposition and metabolism of sulfolane in Harlan Sprague Dawley rats and B6C3F1/N mice and in vitro in hepatocytes from rats, mice, and humans

Sulfolane has been found as a ground water contaminant near refining sites. These studies investigated the in vitro hepatic clearance and in vivo disposition of [14C]sulfolane in rats and mice following a single oral administration (30, 100, or 300 mg/kg) and dermal application (100 mg/kg).
[14C]Sulfolane was well-absorbed in male rats following oral administration and excreted extensively in urine (≥93%). Total radioactivity in tissues at 24 and 48 h was ∼7% and <2%. Disposition pattern was similar in female rats and male and female mice at 100 mg/kg oral dose.
Dermally applied [14C]Sulfolane (covered dose site, 100 mg/kg) was poorly absorbed in male (∼16%) and female (∼19%) rats; absorption increased to 59% when the dose site was uncovered in male rats suggesting ingestion of dose via grooming of the dose site. Dermally applied [14C]sulfolane (100 mg/kg, covered dose site) was well absorbed in male (∼70%) and female (∼80%) mice.
Urinary radiochemical profiles were similar between routes, species, and sexes; the main analytes present in urine were sulfolane and 3-hydroxysulfolane.
Sulfolane was not cleared in hepatocytes from rodents or human suggesting sites other than liver might be involved in metabolism of sulfolane in vivo.

Sulfolane has been found as a ground water contaminant near refining sites. These studies investigated the in vitro hepatic clearance and in vivo disposition of [14C]sulfolane in rats and mice following a single oral administration (30, 100, or 300 mg/kg) and dermal application (100 mg/kg).
[14C]Sulfolane was well-absorbed in male rats following oral administration and excreted extensively in urine (≥93%). Total radioactivity in tissues at 24 and 48 h was ∼7% and <2%. Disposition pattern was similar in female rats and male and female mice at 100 mg/kg oral dose.
Dermally applied [14C]Sulfolane (covered dose site, 100 mg/kg) was poorly absorbed in male (∼16%) and female (∼19%) rats; absorption increased to 59% when the dose site was uncovered in male rats suggesting ingestion of dose via grooming of the dose site. Dermally applied [14C]sulfolane (100 mg/kg, covered dose site) was well absorbed in male (∼70%) and female (∼80%) mice.
Urinary radiochemical profiles were similar between routes, species, and sexes; the main analytes present in urine were sulfolane and 3-hydroxysulfolane.
Sulfolane was not cleared in hepatocytes from rodents or human suggesting sites other than liver might be involved in metabolism of sulfolane in vivo.

研究人员已在炼油厂周边地下水中检出环丁砜（Sulfolane）。本系列研究针对单次口服给药（剂量分别为30、100或300mg/kg）与皮肤给药（剂量为100mg/kg）后，碳-14标记环丁砜（[14C]sulfolane）在大鼠与小鼠体内的体外肝脏清除率及体内处置过程展开探究。
[14C]Sulfolane在雄性大鼠口服给药后吸收良好，且药物经尿液广泛排泄（排泄率≥93%）。给药后24小时与48小时的组织总放射性分别约为7%与低于2%。在100mg/kg口服给药剂量下，雌性大鼠以及雌雄小鼠的体内处置模式与雄性大鼠一致。
皮肤给药（给药部位被遮盖，剂量为100mg/kg）时，雌雄大鼠对碳-14标记环丁砜的吸收均较差（雄性约16%，雌性约19%）；若去除给药部位的遮盖物，雄性大鼠的药物吸收提升至59%，这提示药物可能通过大鼠舔舐给药部位经口摄入。而在给药部位被遮盖的情况下，雌雄小鼠对皮肤给药的碳-14标记环丁砜吸收良好（雄性约70%，雌性约80%）。
不同给药途径、物种与性别间的尿液放射性化学谱图均较为相似；尿液中的主要分析物为环丁砜与3-羟基环丁砜。
啮齿类动物与人类的肝细胞均无法代谢清除环丁砜，这提示体内环丁砜的代谢可能并非仅发生于肝脏，其他组织/器官也可能参与其代谢过程。

研究人员已在炼油厂周边地下水中检出环丁砜（Sulfolane）。本系列研究针对单次口服给药（剂量分别为30、100或300mg/kg）与皮肤给药（剂量为100mg/kg）后，碳-14标记环丁砜（[14C]sulfolane）在大鼠与小鼠体内的体外肝脏清除率及体内处置过程展开探究。
[14C]Sulfolane在雄性大鼠口服给药后吸收良好，且药物经尿液广泛排泄（排泄率≥93%）。给药后24小时与48小时的组织总放射性分别约为7%与低于2%。在100mg/kg口服给药剂量下，雌性大鼠以及雌雄小鼠的体内处置模式与雄性大鼠一致。
皮肤给药（给药部位被遮盖，剂量为100mg/kg）时，雌雄大鼠对碳-14标记环丁砜的吸收均较差（雄性约16%，雌性约19%）；若去除给药部位的遮盖物，雄性大鼠的药物吸收提升至59%，这提示药物可能通过大鼠舔舐给药部位经口摄入。而在给药部位被遮盖的情况下，雌雄小鼠对皮肤给药的碳-14标记环丁砜吸收良好（雄性约70%，雌性约80%）。
不同给药途径、物种与性别间的尿液放射性化学谱图均较为相似；尿液中的主要分析物为环丁砜与3-羟基环丁砜。
啮齿类动物与人类的肝细胞均无法代谢清除环丁砜，这提示体内环丁砜的代谢可能并非仅发生于肝脏，其他组织/器官也可能参与其代谢过程。